[en] X-chromosome exome sequencing was performed to identify the genetic cause of syndromic intellectual disability in two unrelated families with suspected X-linked inheritance. In both families, affected males presented with severe intellectual disability, microcephaly, growth retardation, and epilepsy. A missense mutation (c.777T>G p.(Ile259Met)) and a frameshift mutation (c.1394_1397del p.(Ile465Serfs*4)) were identified in the EIF2S3 gene in the hemizygous state in affected patients, and in the heterozygous states female obligate carriers. A missense mutation in EIF2S3, coding for the gamma-subunit of the translation initiation factor eIF2, was reported once in a family presenting with similar clinical features. Morpholino-based knockdown of the zebrafish EIF2S3 ortholog (eif2s3) recapitulates the human microcephaly and short stature phenotype, supporting the pathogenicity of the identified variants. Our data confirm that EIF2S3 mutation is implicated in a rare, but recognizable, form of syndromic intellectual disability.
Disciplines :
Genetics & genetic processes
Author, co-author :
Moortgat, Stéphanie; Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Charleroi (Gosselies), Belgium. stephanie.moortgat@ipg.be
Désir, Julie; Centre de Génétique Humaine, Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium
Benoit, Valérie ; Université de Liège - ULiège > Département de pharmacie > GIGA-R : Chimie médicale ; Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Charleroi (Gosselies), Belgium
Boulanger, Sébastien; Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Charleroi (Gosselies), Belgium
Pendeville-Samain, Hélène ; Université de Liège - ULiège > Unités de recherche interfacultaires > GIGA-Research
Nassogne, Marie-Cécile; Département de Neuropédiatrie, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Lederer, Damien; Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Charleroi (Gosselies), Belgium
Maystadt, Isabelle; Centre de Génétique Humaine, Institut de Pathologie et de Génétique, Charleroi (Gosselies), Belgium
Language :
English
Title :
Two novel EIF2S3 mutations associated with syndromic intellectual disability with severe microcephaly, growth retardation, and epilepsy.
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